ABSTRACT Background: Cannabis is one of the most widely used substances by children and young adults. While there is accumulating preclinical evidence that exposure to cannabinoids in adolescence has far reaching consequences on neurodevelopment, the effects of early cannabis exposure on the brain has not been adequately studied in humans. Thus, there is a need to assess the impact of cannabis exposure on the developing brain during adolescence using measures that are as proximal to brain function as possible. Oscillatory activity in the gamma (?) band (30-80 Hz) has been shown to be critically involved in brain functions such as attention, and working memory. There is compelling evidence that many features of ? oscillations evolve over childhood and adolescence following specific trajectories that coincide with critical milestones of brain development. The location and modulatory role of cannabinoid receptors type 1 (CB1R) make the endocannabinoid system well poised to influence ? oscillations. In fact, animal studies show that CB1R agonists acutely disrupt ? oscillations and that exposure to cannabinoids in early adolescence, but not adulthood, selectively disrupts ? oscillations measured later during adulthood . Thus, the study of the effect of cannabis on ? oscillations in adolescents has the potential to provide objective cross-sectional and longitudinal information about the effects of cannabis on the developing brain in real time at their inception. Hypothesis: The overarching hypothesis of this exploratory grant proposal is that cannabis-using adolescents (CAN+) will show reductions in evoked and induced ? oscillations as captured by electroencephalography (EEG), compared to cannabis-nave adolescents (CAN-). Furthermore, the neurodevelopmental trajectory (i.e. increase over time) of evoked and induced ? oscillations will be blunted in CAN+. Reductions in evoked and induced ? oscillations are predicted to correlate with deficits in cognitive test performance and academic achievement in CAN+. Methods: In this part cross-sectional and part longitudinal prospective study, an equal number (n=34) of CAN+ and CAN- (13-16 years) will be assessed at baseline, 9 and 18 months. ? oscillations will be recorded with EEG while the subjects engage in two widely used, well-validated tasks to elicit evoked (steady-state response tasks) and induced (Gestalt perception tasks) ? activity. Cognition (CogState battery) and school grade data will be collected. Cross-sectional comparisons (CAN+ vs. CAN-) will be conducted at all time-points for all the measures. Longitudinal age-related changes of ? oscillations of CAN+ and CAN- will be compared across the 3 time points. Correlations between deficits in ? oscillations and both cognitive performance and academic achievement will be obtained.